Recurrent sellar mass after resection of pituitary macroadenoma

Posted on June 17, 2015 by MaryO

A Puerto Rican woman aged 50 years presented to an ophthalmologist with complaints of vision changes, including difficulty seeing images in her peripheral vision in both eyes and difficulty in color perception. Her medical history was significant for menopause at age 43 years, type 2 diabetes and hypertension. She had no prior history of thyroid disease, changes in her weight, dizziness or lightheadedness, headaches, galactorrhea or growth of her hands or feet.

Formal visual fields showed bitemporal superior quadrantopsia, and she was sent to the ED for further evaluation.

Imaging and laboratory tests

A pituitary protocol MRI was performed that showed a large 3 cm x 2 cm x 2.2 cm mass in the pituitary with mild osseous remodeling of the sella turcica and mass effect on the optic chiasm (Figure 1). The mass was isointense with the brain parenchyma on T1-weighted and T2-weighted images and homogeneously enhanced after IV gadolinium contrast administration.

Baseline laboratory samples drawn at 11 p.m. in the ED showed a cortisol of 16.9 µg/dL (nighttime reference range: 3-16 µg/dL), adrenocorticotropic hormone 65 pg/mL (reference range: 6-50 pg/mL), prolactin 19.4 ng/mL (reference range: 5.2-26.5 ng/mL), thyroid-stimulating hormone 1.36 µIU/mL (reference range: 0.35-4.9 µIU/mL), free thyroxine 0.9 ng/dL (reference range: 0.6-1.8 ng/dL), triiodothyronine 85 ng/dL (reference range: 83-160 ng/dL), follicle-stimulating hormone (FSH) 11.1 mIU/mL (postmenopausal reference range: 26.7- 133.4 mIU/mL) and luteinizing hormone (LH) 1.2 mIU/mL (postmenopausal reference range: 5.2-62 mIU/mL).

 

Figure 1. T1-weighted MRI images with and without contrast of the pituitary. Coronal (A) and sagittal (C) images showed a large isodense (with brain parenchyma) 3 cm x 2 cm x 2.2 cm mass (red arrow) in the sella with superior extension to the optic chiasm. After gadolinium contrast, coronal (B) and sagittal (D) images show the mass homogenously enhances consistent with a pituitary adenoma.

Images courtesy of Pavani Srimatkandada, MD.

Given the patient’s high nighttime cortisol and adrenocorticotropic hormone (ACTH) levels, she underwent an overnight dexamethasone suppression test with 1 mg dexamethasone. Her morning cortisol was appropriately suppressed to less than 1 µg/dL, excluding Cushing’s disease.

Pituitary adenoma resection

The patient was diagnosed with a nonsecreting pituitary adenoma with suprasellar extension and optic chiasm compression with visual field deficits. The macroadenoma caused an inappropriately normal LH and FSH in a postmenopausal woman consistent with hypogonadotrophic hypogonadism.

She underwent transnasal transsphenoidal resection of the nonsecreting pituitary adenoma. The dural defect caused by the surgery was patched with an abdominal fat graft with a DuraSeal dura patch. A postoperative MRI showed complete resection of the adenoma with no evaluable tumor in the sella (Figure 2). Her postoperative course was complicated by transient diabetes insipidus requiring intermittent desmopressin; however, this resolved before her discharge from the hospital.

Figure 2. T1-weighted MRI images with contrast. Coronal views before (A) and after (B) transphenoidal tumor resection show complete resolution of the enhancing pituitary mass (A; red arrow) that is replaced with a new hypodense mass in the sella (B; yellow arrow). This mass is filled with cerebrospinal fluid with a residual rim of enhancing tissue. This is consistent with the development of a pseudomeningocele in the sella.

 

Postoperative testing confirmed secondary deficiency of the adrenal, thyroid and ovarian axes requiring hormone therapy. The patient had stable temporal hemianopia in the left eye with improved vision in the right eye.

Recurrent mass detected

One year after surgery, during a routine follow-up appointment, the patient reported no dizziness, lightheadedness, worsening vision changes, rhinorrhea or headache. She had a follow-up MRI of the brain with and without contrast, which showed the interval appearance of a mass in the sella that extended from the sphenoid sinus into the sella and came in contact with the optic nerve (Figure 3).

Figure 3. Axial MRI images of the sella after resection of pituitary adenoma. On T1-weighted images the mass (red arrow) in the sella is hypodense (black) compared with the brain parenchyma. On T2-weighted images, the mass (red arrow) is hyperdense (bright) compared with the brain, consistent with fluid. Cerebrospinal fluid in the sulci on the brain surface and the vitreous fluid within the eye are also hyperintense on T2-weighted images (yellow arrows).

 

On MRI, the mass was isodense with the cerebral spinal fluid (CSF) with a residual rim of enhancing normal pituitary tissue. This appearance is consistent with the postoperative development of a pseudomeningocele and not a solid mass in the sella (Table).

Pseudomeningoceles are abnormal collections of CSF that communicate with the CSF space around the brain; these occur after brain surgery involving duraplasty (incision and repair of the dura). Unlike meningoceles, pseudomeningoceles are not completely encased by a surrounding membrane, and they communicate with the circulating CSF. Similar to CSF, a pseudomeningocele is hypodense (dark) compared with brain on T1-weighted MRI images and hyperdense (bright) on T2-weight images.

 

Pseudomeningocele treatment

Treatment may be conservative or may involve neurosurgical repair if symptomatic. Little published data addresses the development of pseudomeningoceles after transsphenoidal pituitary surgery, but this complication occasionally occurs, especially if the dural incision is large. One study noted that pseudomeningoceles are one of the most common complications after suboccipital decompression for Chiari’s malformation, but the effect of this complication is unclear.

Endocrinologists must recognize that recurrent development of pituitary masses after transsphenoidal pituitary adenoma surgery may not represent regrowth of pituitary tissue, but instead development of a meningocele/pseudomeningocele. Pseudomeningocele can be easily confirmed because this fluid collection has very different MRI characteristics than pituitary adenoma (Table). Given that patients may remain asymptomatic after the development of a pseudomeningocele, periodic MRI imaging, hormonal evaluation and ophthalmologic monitoring of visual fields are required after transsphenoidal pituitary surgery.

References:
  • Hernandez Guilabert PM. Poster No C-1330. Presented at: European Society of Radiology; March 7-11, 2013; Vienna.
  • Parker SL, et al. J Neurosurg. 2013;doi:10.3171/2013.8.JNS122106.
For more information:
  • Stephanie L. Lee, MD, PhD, ECNU, is an associate professor of medicine and associate chief, in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. Lee reports no relevant financial disclosures.
  • Pavani Srimatkandada, MD, is an endocrinology fellow in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Srimatkandada can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118. She reports no relevant financial disclosures.

From http://www.healio.com/endocrinology/thyroid/news/print/endocrine-today/%7B82430fb6-bbe4-4908-a389-447eee8cd005%7D/recurrent-sellar-mass-after-resection-of-pituitary-macroadenoma

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Paediatric cyclical Cushing’s disease due to corticotroph cell hyperplasia

Posted on June 11, 2015 by MaryO

Cushing’s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing’s syndrome has been described in the adult population, but appears to be extremely rare in children.

Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing’s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia. The case is that of a 13-year old boy, presenting with a long history of symptoms and signs suggestive of hypercortisolism, who was found to have cyclical ACTH-dependent hypercortisolism following dynamic pituitary testing and serial late-night salivary cortisol measurements.

The patient underwent endoscopic transsphenoidal resection of the pituitary. Early surgical remission was confirmed by undetectable post-operative morning plasma cortisol levels.

Histology and immunocytochemistry of the resected pituitary tissue showed extensive corticotroph cell hyperplasia.

Conclusion: This report describes a rare case of cyclical Cushing’s disease secondary to corticotroph hyperplasia in a paediatric patient. This highlights the challenging and varied nature of Cushing’s disease and its diagnosis, and the need to keep a differential diagnosis in mind during the diagnostic process.

Author: E. Noctor S. Gupta T. Brown M. Farrell M. Javadpour C. Costigan A. Agha
Credits/Source: BMC Endocrine Disorders 2015, 15:27

From http://7thspace.com/headlines/510543/paediatric_cyclical_cushings_disease_due_to_corticotroph_cell_hyperplasia.html

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Silibinin from milk thistle seeds as novel, non-invasive treatment strategy for Cushing Disease

Posted on June 4, 2015 by MaryO
Silibinin has an outstanding safety profile in humans and is currently used for the treatment of liver disease and poisoning. Scientists at the Max Planck Institute of Psychiatry in Munich discovered in collaboration with scientists from the Helmholtz Zentrum München in cell cultures, animal models and human tumor tissue that silibinin can be applied to treat Cushing Disease, a rare hormone condition caused by a tumor in the pituitary gland in the brain. The researchers have filed a patent and now plan clinical trials using silibinin as a non-invasive treatment strategy. Thus, in future, patients might not have to undergo brain surgery anymore.
Treatment with silibinin, a constituent of milk thistle seeds, alleviated symptoms of Cushing Disease in cell cultures, animal models and human tumor tissue. In future, patients might not have to undergo brain surgery anymore.

Cushing Disease, not to be confused with Cushing’s Syndrome, is caused by a tumor in the pituitary gland in the brain. The tumor secrets increased amounts of the stress hormone adrenocorticotropin (ACTH) followed by cortisol release from the adrenal glands leading to rapid weight gain, elevated blood pressure and muscular weakness. Patients are prone to osteoporosis and infections and may show cognitive dysfunction or even depression. In 80 to 85 % of the patients, the tumor can be removed by uncomfortable brain surgery. For inoperable cases, there is currently only one targeted therapy approved, which unfortunately causes intense side effects such as hyperglycemia in more than 20 % of the patients.

Scientists around Günter Stalla, endocrinologist at the Max Planck Institute of Psychiatry in Munich, have now discovered in cell cultures, animal models and human tumor tissue that a harmless plant extract can be applied to treat Cushing Disease. “Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning,” explains Marcelo Paez-Pereda, leading scientist of the current study published in the renowned scientific journal Nature Medicine. After silibinin treatment, tumor cells resumed normal ACTH production, tumor growth slowed down and symptoms of Cushing Disease disappeared in mice.

In 2013, the Max Planck scientists filed a patent on a broad family of chemical and natural compounds, including silibinin, to treat pituitary tumors. Compared to humans, where only 5.5 in 100,000 people worldwide develop Cushing Disease, this condition is very common in several pets. For example, 4 % of dogs and even 7 % of horses suffer from Cushing Disease. Thus, the researchers now plan to test special formulations with a very pure substance and slow release of the active component silibinin in clinical trials.

Silibinin: Mode of action

“We knew that Cushing Disease is caused by the release of too much ACTH. So we asked ourselves what causes this over production and how to stop it,” says Paez-Pereda. In their first experiments, the researchers found tremendously high amounts of the heat shock protein 90 (HSP90) in tumor tissue from patients with Cushing Disease. In normal amounts, HSP90 helps to correctly fold another protein, the glucocorticoid receptor, which in turn inhibits the production of ACTH. “As there are too many HSP90 molecules in the tumor tissue, they stick to the glucocorticoid receptor,” explains Paez-Pereda. “We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin, we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors, such as lung tumors, acute lymphoblastic leukemia or multiple myeloma,” concludes Paez-Pereda.

From http://www.psych.mpg.de/2034377/PM1507

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Cushing’s Syndrome

Posted on May 22, 2015 by MaryO
Prof André Lacroix, MDcorrespondence,  Richard A Feelders, MD, Constantine A Stratakis, MD, Lynnette K Nieman, MD
Published Online: 21 May 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(14)61375-1

Summary

Chronic exposure to excess glucorticoids results in diverse manifestations of Cushing’s syndrome, including debilitating morbidities and increased mortality.

Genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and adrenocorticotropic hormone (ACTH) secretion from corticotroph or ectopic tumours have been identified. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients.

The therapeutic goal is to normalise tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumour is necessay to allow eventual normalisation of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumour recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess.

However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism need ongoing care.

Read the entire article (there is a fee of $31.50US) here.

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Macroadenoma biochemical behavior in pediatric patients with Cushing’s disease differs from adult cases

Posted on May 15, 2015 by MaryO

Cushing’s disease in children is associated with similar biochemical measures whether the disease is due to macroadenomas or microadenomas, according to a presentation at the AACE 24th Annual Scientific & Clinical Congress.

This contrasts with the disease behavior in adults, in whom macrodenomas demonstrate less glucocorticoid suppression and adrenocorticotropic hormone (ACTH) response to laboratory tests than do microadenomas, according to researchers.

“Children with pituitary macroadenomas are more likely to have the classical response to Cushing’s disease functional testing as microadenomas,”Ricardo Correa, MD, a clinical and research endocrinology fellow at National Institutes of Health, told Endocrine Today.

Correa and colleagues conducted a retrospective review of patients with Cushing’s disease who were younger than 18 years when they were admitted to the NIH between 1997 and 2014. All Cushing’s diagnoses were confirmed by pathology.

Pituitary macroadenoma was identified in 13 patients (69% female) and microadenoma in 74 (58% female). The groups had similar mean age (14 years) and BMI (31.8 kg/m2 and 30.2 kg/m2 for macroadenoma and microadenoma, respectively). The macroadenoma group had a median (25% to 75%) 24-hour urine free cortisol of  263.60 mcg/24 hr (range 170.7-528) compared with 371.6 mcg/ 24 hr (range 244.2-625.3) in the microadenoma group (P = 0.47). Median 24-hr urinary 17-hydroxysteroid excretion in the macroadenoma group was 12.6 mg/24 hr (range 8.9-42.5) and 31.6 mg/24 hr (range 4.3-39.9) in the microadenoma group.

Mean morning serum cortisol was 38.9 ± 40.4 mcg/dL compared with  20.2 ± 15.8 mcg/dL in the macroademona and microadenoma groups, respectively (P = 0.16). Mean morning basal plasma ACTH was 106.3 ± 112.3 pg/mL compared with 49.9±44.3 pg/mL for the macroadenoma and microadenoma groups, respectively (P = 0.11), while ACTH responses to the ovine corticotropin-releasing hormone test revealed no statistically significant differences. Using the high dose dexamethasone suppression test, 58% (7/12) suppressed more than 69% in the macroadenoma group compared to 69% (44/64) in the microadenoma group (P = .51).

“Studies in adult patients have demonstrated that macroadenomas have less glucocorticoid suppressibility after the high-dose dexamethasone suppression test and attenuated ACTH response to CRH compared to pituitary microadenomas,” according to Correa. “However, the present study shows that this is not true in children; although patients with macroadenomas had a tendency for higher baseline serum ACTH and cortisol levels, their responses to dynamic testing were similar to those with microadenomas.”

Reference:

Correa R, et al. Abstract #803. Presented at: AACE 24th Annual Scientific & Clinical Congress; May 13-17, 2015; Nashville, Tenn.

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7Bb4fbf36f-ac88-4eff-9278-90f0a8d1aec2%7D/macroadenoma-biochemical-behavior-in-pediatric-patients-with-cushings-disease-differs-from-adult-cases?sc_trk=internalsearch

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